A Novel Supplement Regimen for Healthy Aging: A Case Series

Main Article Content

Joseph Keenan, MD

Abstract

Objective: This case series aims to evaluate a novel supplement regimen for healthy aging in older adults, assess its potential to reduce reliance on prescription drugs like metformin and statins, and inform the design of a larger clinical trial.


Background: The convergence of an aging population and increasing prevalence of age-related chronic diseases continues to strain limited healthcare resources and exert financial pressures on healthcare systems and individuals alike. For this reason, cost-effective, readily available solutions are needed more than ever to help reduce the disease burden among older adults.


Methods: Participants included 10 men and women, aged 62-91 years, who were given a supplement regimen providing niacin (extended-release tablets), dihydroberberine (sustained-release tablets), taxifolin (sustained-release tablets), and mixed tocotrienols (immediate-release softgels) along with diet instructions. Participants were required to share the study protocol with their personal doctors, and agree to periodic in-person home visits. Blood tests (blood lipid profile, comprehensive metabolic profile, uric acid, homocysteine, and HbA1c) were completed at baseline and repeated at 6 weeks, 12 weeks and quarterly thereafter to monitor benefits and possible adverse side effects, unless abnormal tests warranted closer monitoring. Participants underwent cognitive and well-being assessments at baseline and study completion.


Results: Supplement intervention lasted 16 months, on average, resulting in clinically relevant reductions in total cholesterol, LDL cholesterol, and triglycerides, and an increase in HDL cholesterol. All participants with elevated Lp(a) levels at baseline (n=3) experienced reductions by study completion. All seven participants on statin drugs at baseline were able to discontinue use while achieving similar or better lipid outcomes after withdrawal. Only one participant resumed statin use, despite lipid improvements, due to digestive issues. Participants completing the self-reported assessment of well-being (n=10) reported generally stable or positive physical and mental function compared to baseline. Drop-outs were prevented with the successful management of transient side effects.


Conclusions: While more research is needed, this case series validates the therapeutic potential of a novel dietary supplement regimen to promote healthy aging in older adults, including treating dyslipidemia, promoting well-being, and reducing prescription drug use, as well as inform the design of a larger clinical trial.

Keywords: niacin, nicotinic acid, niacinamide, dihydroberberine, taxifolin, mixed tocotrienols, cardiovascular disease, healthy aging

Article Details

How to Cite
KEENAN, Joseph. A Novel Supplement Regimen for Healthy Aging: A Case Series. Medical Research Archives, [S.l.], v. 12, n. 10, oct. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/5830>. Date accessed: 03 dec. 2024. doi: https://doi.org/10.18103/mra.v12i10.5830.
Section
Research Articles

References

1. . Patwardhan V, Gil GF, Arrieta A, et al. Differences across the lifespan between females and males in the top 20 causes of disease burden globally: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Public Health. 2024;9(5):e282-e294. doi:10.1016/S2468-2667(24)00053-7
2. . Keenan J. The niacin rebirth: revisiting the potential of nicotinic acid therapy for cardiovascular disease and niacin supplementation for healthy aging. Med Res Arch. 2024;12(7):1-9. doi:10.18103/mra.v12i7.5521
3. . AIM-HIGH Investigators. The role of niacin in raising high-density lipoprotein cholesterol to reduce cardiovascular events in patients with atherosclerotic cardiovascular disease and optimally treated low-density lipoprotein cholesterol Rationale and study design. The Atherothrombosis Intervention in Metabolic syndrome with low HDL/high triglycerides: Impact on Global Health outcomes (AIM-HIGH). Am Heart J. 2011;161(3):471-477.e2. doi:10.1016/j.ahj.2010.11.017
4. . HPS2-THRIVE Collaborative Group. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. Eur Heart J. 2013;34(17):1279-1291. doi:10.1093/eurheartj/eht055
5. . D'Andrea E, Hey SP, Ramirez CL, Kesselheim AS. Assessment of the role of niacin in managing cardiovascular disease outcomes: a systematic review and meta-analysis. JAMA Netw Open. 2019;2(4):e192224. doi:10.1001/jamanetworkopen.2019.2224
6. . CW. Niacin in patients with chronic kidney disease: is it effective and safe?. Kidney Res Clin Pract. 2013;32(1):1-2. doi:10.1016/j.krcp.2013.02.001
7. . Wuerch E, Urgoiti GR, Yong VW. The promise of niacin in neurology. Neurotherapeutics. 2023;20(4):1037-1054. doi:10.1007/s13311-023-01376-2
8. . McReynolds MR, Chellappa K, Baur JA. Age-related NAD+ decline. Exp Gerontol. doi:10.1016/j.exger.2020.110888
9. . Tribble JR, Otmani A, Sun S, et al. Nicotinamide provides neuroprotection in glaucoma by protecting against mitochondrial and metabolic dysfunction. Redox Biol. 2021;43:101988. doi:10.1016/j.redox.2021.101988
10. . Hui F, Tang J, Williams PA, et al. Improvement in inner retinal function in glaucoma with nicotinamide (vitamin B3) supplementation: a crossover randomized clinical trial. Clin Exp Ophthalmol. 2020;48(7):903-914. doi:10.1111/ceo.13818
11. . Feng R, Shou JW, Zhao ZX, et al. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep. 2015;5:12155. doi:10.1038/srep12155
12. . Song D, Hao J, Fan D. Biological properties and clinical applications of berberine. Front Med. 2020;14(5):564-582. doi:10.1007/s11684-019-0724-6
13. . Imenshahidi M, Hosseinzadeh H. Berberine and barberry (Berberis vulgaris): a clinical review. Phytother Res. 2019;33(3):504-523. doi:10.1002/ptr.6252
14. . Bibak B, Shakeri F, Keshavarzi Z, et al. Anticancer mechanisms of berberine: a good choice for glioblastoma multiforme therapy. Curr Med Chem. 2022;29(26):4507-4528. doi:10.2174/0929867329666220224112811
15. . Ke X, Zhang R, Li P, et al. Hydrochloride Berberine ameliorates alcohol-induced liver injury by regulating inflammation and lipid metabolism [published correction appears in Biochem Biophys Res Commun. 2022 Aug 20;617(Pt 1):68-69. doi: 10.1016/j.bbrc.2022.05.077]. Biochem Biophys Res Commun. 2022;610:49-55. doi:10.1016/j.bbrc.2022.04.009
16. . Warowicka A, Nawrot R, Goździcka-Józefiak A. Antiviral activity of berberine. Arch Virol. 2020;165(9):1935-1945. doi:10.1007/s00705-020-04706-3
17. . Das A, Baidya R, Chakraborty T, Samanta AK, Roy S. Pharmacological basis and new insights of taxifolin: a comprehensive review. Biomed Pharmacother. 2021;142:112004. doi:10.1016/j.biopha.2021.112004
18. . Kanchi MM, Shanmugam MK, Rane G, Sethi G, Kumar AP. Tocotrienols: the unsaturated sidekick shifting new paradigms in vitamin E therapeutics [published correction appears in Drug Discov Today. 2019 Jul;24(7):1421. doi: 10.1016/j.drudis.2018.02.010]. Drug Discov Today. 2017;22(12):1765-1781. doi:10.1016/j.drudis.2017.08.001
19. . Naomi R, Shafie NH, Kaniappan P, Bahari H. An interactive review on the role of tocotrienols in the neurodegenerative disorders. Front Nutr. 2021;8:754086. doi:10.3389/fnut.2021.754086
20. . Gopalan Y, Shuaib IL, Magosso E, et al. Clinical investigation of the protective effects of palm vitamin E tocotrienols on brain white matter. Stroke. 2014;45(5):1422-1428. doi:10.1161/STROKEAHA.113.004449
21. . Zuo S, Wang G, Han Q, et al. The effects of tocotrienol supplementation on lipid profile: a meta-analysis of randomized controlled trials. Complement Ther Med. 2020;52:102450. doi:10.1016/j.ctim.2020.102450
22. . O'Byrne D, Grundy S, Packer L, et al. Studies of LDL oxidation following alpha-, gamma-, or delta-tocotrienyl acetate supplementation of hypercholesterolemic humans. Free Radic Biol Med. 2000;29(9):834-845. doi:10.1016/s0891-5849(00)00371-3
23. . Radhakrishnan A, Tudawe D, Chakravarthi S, Chiew GS, Haleagrahara N. Effect of γ-tocotrienol in counteracting oxidative stress and joint damage in collagen-induced arthritis in rats. Exp Ther Med. 2014;7(5):1408-1414. doi:10.3892/etm.2014.1592
24. . Lewis ED, Meydani SN, Wu D. Regulatory role of vitamin E in the immune system and inflammation. IUBMB Life. 2019;71(4):487-494. doi:10.1002/iub.1976
25. . Lu Y, Zhang Y, Pan Z, et al. Potential “therapeutic” effects of tocotrienol-rich fraction (TRF) and carotene “against” bleomycin-induced pulmonary fibrosis in rats via TGF-β/Smad, PI3K/Akt/mTOR and NF-κB signaling pathways. Nutrients. 2022;14(5):1094. doi:10.3390/nu14051094
26. . Sailo BL, Banik K, Padmavathi G, Javadi M, Bordoloi D, Kunnumakkara AB. Tocotrienols: the promising analogues of vitamin E for cancer therapeutics. Pharmacol Res. 2018;130:259-272. doi:10.1016/j.phrs.2018.02.017
27. . Zainal Z, Khaza'ai H, Kutty Radhakrishnan A, Chang SK. Therapeutic potential of palm oil vitamin E-derived tocotrienols in inflammation and chronic diseases: evidence from preclinical and clinical studies. Food Res Int. 2022;156:111175. doi:10.1016/j.foodres.2022.111175
28. . Poon IO, Chow DS, Liang D. Dissolution profiles of nonprescription extended-release niacin and inositol niacinate products. Am J Health Syst Pharm. 2006;63(21):2128-2134. doi:10.2146/ajhp060089
29. . Qu H, Guo M, Chai H, Wang WT, Gao ZY, Shi DZ. Effects of coenzyme Q10 on statin-induced myopathy: an updated meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7(19):e009835. doi:10.1161/JAHA.118.009835
30. . Saxon DR, Eckel RH. Statin intolerance: a literature review and management strategies. Prog Cardiovasc Dis. 2016;59(2):153-164. doi:10.1016/j.pcad.2016.07.009
31. . Prasanna P, Liu S, Silverman D. Lipophilic statins in subjects with early mild cognitive impairment: associations with conversion to dementia and decline in posterior cingulate brain metabolism in a long-term prospective longitudinal multi-center study. J Nucl Med. 2021;62(supp 1). Abstract 102. doi.org/10.1002/alz.069394
32. . Zhu L, Fang Y, Gao B, et al. Effect of an increase in Lp(a) following statin therapy on cardiovascular prognosis in secondary prevention population of coronary artery disease [published correction appears in BMC Cardiovasc Disord. 2022 Dec 30;22(1):577. doi: 10.1186/s12872-022-03027-4]. BMC Cardiovasc Disord. 2022;22(1):474. doi:10.1186/s12872-022-02932-y
33. . Björnson E, Adiels M, Taskinen MR, et al. Lipoprotein(a) is markedly more atherogenic than LDL: an apolipoprotein b-based genetic analysis. J Am Coll Cardiol. 2024;83(3):385-395. doi:10.1016/j.jacc.2023.10.039